Genetic Variant THBS2:c.892-45T>G (chr6-169240637-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003247.5(THBS2):c.892-45T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 1,587,562 control chromosomes in the GnomAD database, including 7,106 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 2716 hom., cov: 33)

Exomes 𝑓: 0.054 ( 4390 hom. )

Consequence

THBS2
NM_003247.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.541

Publications

3 publications found

Variant links:

Genes affected

THBS2 (HGNC:11786): (thrombospondin 2) The protein encoded by this gene belongs to the thrombospondin family. It is a disulfide-linked homotrimeric glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein has been shown to function as a potent inhibitor of tumor growth and angiogenesis. Studies of the mouse counterpart suggest that this protein may modulate the cell surface properties of mesenchymal cells and be involved in cell adhesion and migration. [provided by RefSeq, Jul 2008]

THBS2 links:

THBS2-AS1 (HGNC:56059): (THBS2 antisense RNA 1)

THBS2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003247.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
THBS2	NM_003247.5	MANE Select	c.892-45T>G	intron	N/A	NP_003238.2
THBS2	NM_001381939.1		c.892-45T>G	intron	N/A	NP_001368868.1	A0A7I2V585
THBS2	NM_001381942.1		c.661-45T>G	intron	N/A	NP_001368871.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
THBS2	ENST00000617924.6	TSL:1 MANE Select	c.892-45T>G	intron	N/A	ENSP00000482784.1	P35442
THBS2	ENST00000366787.7	TSL:1	c.892-45T>G	intron	N/A	ENSP00000355751.3	P35442
THBS2	ENST00000649844.1		c.892-45T>G	intron	N/A	ENSP00000497834.1	A0A3B3ITK0

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20722

AN:

152130

Hom.:

2712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.0758

Gnomad AMR

AF:

0.0893

Gnomad ASJ

AF:

0.0406

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.0540

Gnomad FIN

AF:

0.0620

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0398

Gnomad OTH

AF:

0.111

GnomAD2 exomes

AF:

0.0841

AC:

20253

AN:

240894

AF XY:

0.0771

show subpopulations

Gnomad AFR exome

AF:

0.356

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.0340

Gnomad EAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.0577

Gnomad NFE exome

AF:

0.0389

Gnomad OTH exome

AF:

0.0714

GnomAD4 exome

AF:

0.0536

AC:

76921

AN:

1435314

Hom.:

4390

Cov.:

AF XY:

0.0526

AC XY:

37388

AN XY:

710176

show subpopulations

African (AFR)

AF:

0.360

AC:

11848

AN:

32914

American (AMR)

AF:

0.102

AC:

4400

AN:

42972

Ashkenazi Jewish (ASJ)

AF:

0.0360

AC:

919

AN:

25516

East Asian (EAS)

AF:

0.184

AC:

7192

AN:

38988

South Asian (SAS)

AF:

0.0531

AC:

4420

AN:

83272

European-Finnish (FIN)

AF:

0.0561

AC:

2958

AN:

52728

Middle Eastern (MID)

AF:

0.0574

AC:

326

AN:

5676

European-Non Finnish (NFE)

AF:

0.0371

AC:

40639

AN:

1094056

Other (OTH)

AF:

0.0713

AC:

4219

AN:

59192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3445

6890

10336

13781

17226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1792

3584

5376

7168

8960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.136

AC:

20758

AN:

152248

Hom.:

2716

Cov.:

AF XY:

0.134

AC XY:

10011

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.345

AC:

14323

AN:

41498

American (AMR)

AF:

0.0899

AC:

1375

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0406

AC:

141

AN:

3472

East Asian (EAS)

AF:

0.185

AC:

960

AN:

5176

South Asian (SAS)

AF:

0.0536

AC:

259

AN:

4832

European-Finnish (FIN)

AF:

0.0620

AC:

658

AN:

10620

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0398

AC:

2707

AN:

68030

Other (OTH)

AF:

0.112

AC:

236

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

776

1553

2329

3106

3882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0902

Hom.:

306

Bravo

AF:

0.150

Asia WGS

AF:

0.124

AC:

429

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.10

(source)

DANN

Benign

0.51

PhyloP100

-0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over